Diabetes mellitus is a disease of major global importance, increasing in frequency at almost epidemic rates, such that the worldwide prevalence in 2006 is 170 million people and predicted to at least double over the next 10-15 years. Diabetes is characterized by a chronically raised blood glucose concentration (hyperglycemia), due to a relative or absolute lack of the pancreatic hormone, insulin. Within the healthy pancreas, beta cells, located in the islets of Langerhans, continuously produce and secrete insulin in correspondence to blood glucose levels, maintaining near-constant glucose levels in the body.
Much of the burden of the disease to the user/patient, caregivers (e.g., physicians, Certified Diabetes Educators) and to health care resources is due to long-term tissue complications, which affect both small blood vessels (microangiopathy, causing eye, kidney and nerve damage) and large blood vessels (causing accelerated atherosclerosis, with increased rates of coronary heart disease, peripheral vascular disease and stroke). The Diabetes Control and Complications Trial (DCCT) demonstrated that development and progression of the chronic complications of diabetes are greatly related to the degree of altered glycemia as quantified by determinations of glycohemoglobin (HbA1c) [DCCT Trial, N Engl J Med 1993; 329: 977-986, UKPDS Trial, Lancet 1998; 352: 837-853. BMJ 1998; 317, (7160): 703-13 and the EDIC Trial, N Engl J Med 2005; 353, (25): 2643-53]. Thus, maintaining normoglycemia by frequent glucose measurements and adjustment of insulin delivery accordingly can be of utmost importance.
Insulin pumps deliver rapid-acting insulin (e.g., Lispro, Aspart, etc.) 24 hours a day through a catheter placed under the skin. The total daily insulin dose (TDD) can be divided into basal and bolus doses. Insulin bolus doses are delivered before or after meals to counteract consumable intake such as carbohydrates loads or during periods of high blood glucose levels. The dose of the delivered bolus depends on the following parameters:                amount of carbohydrates (Carbs) to be consumed;        carbohydrate-to-insulin ratio (CIR)—amount of carbohydrates balanced by one unit of insulin measured in grams per one unit of insulin;        insulin sensitivity (IS)—amount of blood glucose lowered by one unit of insulin measured in mg/dL (milligrams/deciliter) per one unit of insulin;        current blood glucose levels (CBG), measured in mg/dL. The term “current” as in CBG relates to the BG level measured about the time of the bolus delivery (e.g., within 10 minutes prior to the bolus delivery);        target blood glucose levels (TBG) desired blood glucose level measured in mg/dL; and        residual insulin (RI) amount of stored active insulin remaining in the body of the patient after a recent bolus delivery (also known as bolus on board or BOB).        
Conventional insulin pumps provide bolus dose recommendations that are based on the above mentioned parameters according to the following formula (hereinafter the “formula”):
      Recommended    ⁢                  ⁢    bolus    =                    (                  Carbs          /          CIR                )                    ︸                  “                      Food            ⁢                                                  ⁢            estimate                    ”                      +                            (                      CBG            -            TBG                    )                /        IS                    ︸                  “                      Correction            ⁢                                                  ⁢            estimate                    ”                      -    RI  
For a non-meal related correction bolus, when the blood glucose level (BG) is out of target, the formula is simplified because carbs and optionally residual insulin can be irrelevant and thus not taken into consideration. Then, the formula can be degenerated as follows:Recommended bolus(correction bolus)=(CBG−TBG)/IS.
The above mentioned variables may be also considered in the bolus recommendation feature described in co-owned U.S. publication no. US2008/0234663 and international patent application no. PCT/IL2009/000454 (published as WO2009/133558), the disclosures of which are incorporated herein by reference in their entireties. This bolus recommendation feature comprises sets of grids of ranges of carbohydrate and blood glucose level. Each grid corresponds to a different combination of IS, CIR, and TBG. Additional grids correspond to selected bolus doses and residual insulin values. The final recommended dose is related to a value that is substantially equivalent to the selected bolus dose minus the RI.
Basal insulin is delivered continuously over 24 hours, and maintains blood glucose levels in a specific range (e.g., between meals and overnight). Diurnal basal rates can be pre-programmed or manually changed according to various daily activities (e.g., walking, sleeping, and sport activity), illness and the like. The basal insulin rate/dose may also depend on the user's IS value.
It is apparent to one skilled in the art that accurate IS values are critical for maintaining euglycemia for diabetic patients. IS can be essential in determination of the administered basal dose and the administered bolus dose, especially that of the correction bolus dose.
Typically, the majority of type 1 diabetes patients use a single IS value, assuming that IS has a constant value (i.e., does not change over time) which is independent and does not change upon other occurrences and/or factors.
Alternatively, different IS values are used in different time slots of the day. For example, pump users may set a greater IS value in the evening hours after daily exercise since the sensitivity to insulin increases when physically active.